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1.
Jpn J Infect Dis ; 75(4): 398-402, 2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34980710

RESUMO

The circulation of avian influenza A viruses in poultry is a public health concern due to the potential transmissibility and severity of these viral infections. Monitoring the susceptibility of these viruses to antivirals is important for developing measures to strengthen the level of preparedness against influenza pandemics. However, drug susceptibility information on these viruses is limited. Here, we determined the susceptibilities of avian influenza A(H5N1), A(H5N2), A(H5N8), A(H7N7), A(H7N9), A(H9N1), and A(H9N2) viruses isolated in Japan to the antivirals approved for use there: an M2 inhibitor (amantadine), neuraminidase inhibitors (oseltamivir, peramivir, zanamivir, and laninamivir) and RNA polymerase inhibitors (baloxavir and favipiravir). Genotypic methods that detect amino acid substitutions associated with antiviral resistance and phenotypic methods that assess phenotypic viral susceptibility to drugs have revealed that these avian influenza A viruses are susceptible to neuraminidase and RNA polymerase inhibitors. These results suggest that neuraminidase and RNA polymerase inhibitors currently approved in Japan could be a treatment option against influenza A virus infections in humans.


Assuntos
Farmacorresistência Viral , Influenza Aviária , Influenza Humana , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , RNA Polimerases Dirigidas por DNA , Farmacorresistência Viral/genética , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Humanos , Virus da Influenza A Subtipo H5N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H5N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H7N7/efeitos dos fármacos , Subtipo H7N9 do Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A Subtipo H9N2/efeitos dos fármacos , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Japão/epidemiologia , Neuraminidase/genética , Neuraminidase/metabolismo , Oseltamivir/farmacologia , Oseltamivir/uso terapêutico , Aves Domésticas
2.
Sci Rep ; 11(1): 9427, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33941825

RESUMO

Influenza viruses cause significant morbidity and mortality worldwide. Long-term or frequent use of approved anti-influenza agents has resulted in drug-resistant strains, thereby necessitating the discovery of new drugs. In this study, we found aprotinin, a serine protease inhibitor, as an anti-influenza candidate through screening of compound libraries. Aprotinin has been previously reported to show inhibitory effects on a few influenza A virus (IAV) subtypes (e.g., seasonal H1N1 and H3N2). However, because there were no reports of its inhibitory effects on the other types of influenza viruses, we investigated the inhibitory effects of aprotinin in vitro on a wide range of influenza viruses, including avian and oseltamivir-resistant influenza virus strains. Our cell-based assay showed that aprotinin had inhibitory effects on seasonal human IAVs (H1N1 and H3N2 subtypes), avian IAVs (H5N2, H6N5, and H9N2 subtypes), an oseltamivir-resistant IAV, and a currently circulating influenza B virus. We have also confirmed its activity in mice infected with a lethal dose of influenza virus, showing a significant increase in survival rate. Our findings suggest that aprotinin has the capacity to inhibit a wide range of influenza virus subtypes and should be considered for development as a therapeutic agent against influenza.


Assuntos
Antivirais/farmacologia , Aprotinina/farmacologia , Avaliação Pré-Clínica de Medicamentos , Infecções por Orthomyxoviridae/tratamento farmacológico , Inibidores de Serina Proteinase/farmacologia , Animais , Linhagem Celular , Cães , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/crescimento & desenvolvimento , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/crescimento & desenvolvimento , Vírus da Influenza A Subtipo H5N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H5N2/crescimento & desenvolvimento , Vírus da Influenza A Subtipo H9N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H9N2/crescimento & desenvolvimento , Vírus da Influenza B/efeitos dos fármacos , Vírus da Influenza B/crescimento & desenvolvimento , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos C57BL
3.
Antiviral Res ; 182: 104886, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32750468

RESUMO

Neuraminidase inhibitors (NAIs) are antiviral agents recommended worldwide to treat or prevent influenza virus infections in humans. Past influenza virus pandemics seeded by zoonotic infection by avian influenza viruses (AIV) as well as the increasing number of human infections with AIV have shown the importance of having information about resistance to NAIs by avian NAs that could cross the species barrier. In this study we introduced four NAI resistance-associated mutations (N2 numbering) previously found in human infections into the NA of three current AIV subtypes of the H5Nx genotype that threaten the poultry industry and human health: highly pathogenic H5N8, H5N6 and H5N2. Using the established MUNANA assay we showed that a R292K substitution in H5N6 and H5N2 viruses significantly reduced susceptibility to three licenced NAIs: oseltamivir, zanamivir and peramivir. In contrast the mutations E119V, H274Y and N294S had more variable effects with NAI susceptibility being drug- and strain-specific. We measured the replicative fitness of NAI resistant H5N6 viruses and found that they replicated to comparable or significantly higher titres in primary chicken cells and in embryonated hens' eggs as compared to wild type - despite the NA activity of the viral neuraminidase proteins being reduced. The R292K and N294S drug resistant H5N6 viruses had single amino acid substitutions in their haemagglutinin (HA): Y98F and A189T, respectively (H3 numbering) which reduced receptor binding properties possibly balancing the reduced NA activity seen. Our results demonstrate that the H5Nx viruses can support drug resistance mutations that confer reduced susceptibility to licenced NAIs and that these H5N6 viruses did not show diminished replicative fitness in avian cell cultures. Our results support the requirement for on-going surveillance of these strains in bird populations to include motifs associated with human drug resistance.


Assuntos
Antivirais/farmacologia , Farmacorresistência Viral/genética , Inibidores Enzimáticos/farmacologia , Vírus da Influenza A Subtipo H5N2/efeitos dos fármacos , Neuraminidase/antagonistas & inibidores , Motivos de Aminoácidos , Substituição de Aminoácidos , Animais , Células Cultivadas , Galinhas , Hemaglutininas Virais/genética , Vírus da Influenza A Subtipo H5N2/genética , Influenza Aviária/virologia , Neuraminidase/genética , Proteínas Virais/genética , Replicação Viral/efeitos dos fármacos , Zigoto/virologia
4.
J Vet Med Sci ; 78(9): 1405-1411, 2016 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-27193820

RESUMO

Viral neuraminidase inhibitors are widely used as synthetic anti-influenza drugs for the prevention and treatment of influenza. However, drug-resistant influenza A virus variants, including H5N1 highly pathogenic avian influenza viruses (HPAIVs), have been reported. Therefore, the discovery of novel and effective antiviral agents is warranted. We screened the antiviral effects of 11 herbal tea extracts (hibiscus, black tea, tencha, rosehip tea, burdock tea, green tea, jasmine tea, ginger tea, lavender tea, rose tea and oak tea) against the H5N1 HPAIV in vitro. Among the tested extracts, only the hibiscus extract and its fractionated extract (frHibis) highly and rapidly reduced the titers of all H5 HPAIVs and low pathogenic AIVs (LPAIVs) used in the pre-treatment tests of Madin-Darby canine kidney (MDCK) cells that were inoculated with a mixture of the virus and the extract. Immunogold electron microscopy showed that anti-H5 monoclonal antibodies could not bind to the deformed H5 virus particles pretreated with frHibis. In post-treatment tests of MDCK cells cultured in the presence of frHibis after infection with H5N1 HPAIV, the frHibis inhibited viral replication and the expression of viral antigens and genes. Among the plants tested, hibiscus showed the most prominent antiviral effects against both H5 HPAIV and LPAIV.


Assuntos
Althaea , Antivirais/farmacologia , Hibiscus , Virus da Influenza A Subtipo H5N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H5N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H5N8/efeitos dos fármacos , Extratos Vegetais/farmacologia , Chá , Animais , Camellia sinensis , Cães , Virus da Influenza A Subtipo H5N1/fisiologia , Vírus da Influenza A Subtipo H5N2/fisiologia , Vírus da Influenza A Subtipo H5N8/fisiologia , Jasminum , Lavandula , Células Madin Darby de Rim Canino/virologia , Microscopia Eletrônica , Quercus , Rosa , Rubus , Replicação Viral/efeitos dos fármacos
5.
Arch Med Res ; 46(1): 8-16, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25523147

RESUMO

BACKGROUND AND AIMS: Influenza virus infections are serious public health concerns worldwide that cause considerable mortality and morbidity. Moreover, the emergence of resistance to anti-influenza viral agents underscores the need to develop new anti-influenza viral agents and novel treatment strategies. Recently, we identified anti-influenza viral activity of manuka honey. Therefore, we hypothesized that methylglyoxal (MGO), a key component of manuka honey, may impart anti-influenza viral activity. The aim of this study was to evaluate the anti-influenza viral activity of MGO and its potential in combination treatments with neuraminidase (NA) inhibitors. METHODS: MDCK cells were used to evaluate anti-influenza viral activity. To evaluate the mechanism of MGO, plaque inhibition assays were performed. The synergistic effects of MGO and viral NA inhibitors were tested. RESULTS: MGO inhibited influenza virus A/WSN/33 replication 50% inhibitory concentration = 240 ± 190 µM; 50% cytotoxic concentration = 1.4 ± 0.4 mM; selective index (SI) = 5.8, which is related to its virucidal effects. Moreover, we found that MGO showed promising activity against various influenza strains. A synergistic effect was observed by a marked increase in SI of NA inhibitors at ∼1/100(th) of their single usage. A synergistic effect of MGO and oseltamivir was also observed against oseltamivir-resistant virus. CONCLUSIONS: Our results showed that MGO has potent inhibitory activity against influenza viruses and also enhanced the effect of NA inhibitors. Thus, the co-administration of MGO and NA inhibitors should be considered for treatment of influenza virus infections.


Assuntos
Antivirais/farmacologia , Vírus da Influenza A/efeitos dos fármacos , Neuraminidase/antagonistas & inibidores , Oseltamivir/farmacologia , Aldeído Pirúvico/farmacologia , Animais , Cães , Sinergismo Farmacológico , Quimioterapia Combinada , Inibidores Enzimáticos/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H5N2/efeitos dos fármacos , Concentração Inibidora 50 , Células Madin Darby de Rim Canino , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/virologia , Replicação Viral/efeitos dos fármacos
6.
Tsitologiia ; 56(3): 241-7, 2014.
Artigo em Russo | MEDLINE | ID: mdl-25509421

RESUMO

Influenza is a respiratory infection widely spread around the world. Influenza complications are various in nature and in most cases involve the excessive proliferation of cells in respiratory tract as a factor of pathogenesis. In the present work the efficacy of the use of apoptosis inducer 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphtalenecarboxylic acid (AHPN) for prophylaxis of chronic damage on the stage of post- influenza pneumonia has been studied. Mice were infected with influenza virus A/mallard/Pennsylvania/10218/84(H5N2) with further study of the level of influenza virus reproduction in the lungs, specific mortality of animals and morphology of the foci of post-influenza pneumonia on the 15th day post inoculation. AHPN was shown to decrease the infectious activity of the virus in the lungs by 1.2-1.5 log10 EID50/0.2 mL depending on the dose as compared to the control group, in a weak decrease in mortality of animals (protection index was 12.5-37.5%). The application of AHPN restricted both the proliferative and infiltrative component in chronic post-influenza lesions. It demonstrated the most pronounced effect on the lung morphology when applied on days 4 to 7 post inoculation, i. e. in the period of maximal activation of inflammatory tissue infiltration and regeneration of bronchiolar epithelium. In conclusion, the use of apoptosis inducers can partially prevent the development of chronic post-influenza lesions with proliferative component.


Assuntos
Antineoplásicos/farmacologia , Células Epiteliais/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Infecções por Orthomyxoviridae/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Mucosa Respiratória/efeitos dos fármacos , Retinoides/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células , Relação Dose-Resposta a Droga , Células Epiteliais/patologia , Células Epiteliais/virologia , Vírus da Influenza A Subtipo H5N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H5N2/crescimento & desenvolvimento , Pulmão/patologia , Pulmão/virologia , Camundongos , Infecções por Orthomyxoviridae/complicações , Infecções por Orthomyxoviridae/mortalidade , Infecções por Orthomyxoviridae/patologia , Pneumonia Viral/etiologia , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia , Mucosa Respiratória/patologia , Mucosa Respiratória/virologia , Análise de Sobrevida , Fatores de Tempo , Carga Viral/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
7.
Drug Discov Ther ; 7(5): 189-95, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24270383

RESUMO

Influenza virus infection is a major public health problem that leads to significant morbidity and mortality. The emergence of resistance to the currently available anti-influenza agents has necessitated the development of new drugs with novel targets. Studying known ethno-medicinal plants is a promising approach for the discovery of new antiviral compounds. Alchemilla mollis is used in traditional medicine in Europe for different indications, including minimizing the symptoms of a sore throat. In this study, we found that A. mollis extract has anti-influenza activity, and investigated the mechanism underlying its inhibition of influenza virus replication. Plaque assays demonstrated that treatment of cells with A. mollis extract prior to infection did not inhibit influenza virus infection. However, plaque formation was markedly reduced when infected cells were overlaid with an agarose gel containing A. mollis extract. In addition, exposure of the virus to A. mollis extract prior to infection and treatment of cells during virus infection significantly suppressed plaque formation. Influenza virus-induced hemagglutination of chicken red blood cells was inhibited by A. mollis extract treatment. The inhibitory effect was observed against influenza A virus subtypes H1N1, H3N2, and H5N2. These findings suggest that A. mollis extract has virucidal or neutralizing activity against influenza virus particles. Furthermore, inhibitory effect of zanamivir synergistically increased after combination with A. mollis extract. Our results suggest that A. mollis extract has the potential to be developed as an antiinfluenza agent.


Assuntos
Alchemilla/química , Antivirais/farmacologia , Extratos Vegetais/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Antivirais/administração & dosagem , Galinhas , Cães , Sinergismo Farmacológico , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Testes de Inibição da Hemaglutinação , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H5N2/efeitos dos fármacos , Influenza Humana/tratamento farmacológico , Células Madin Darby de Rim Canino , Medicina Tradicional , Orthomyxoviridae/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Zanamivir/administração & dosagem , Zanamivir/farmacologia
8.
Antiviral Res ; 100(1): 90-7, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23911991

RESUMO

Influenza viruses are important pathogens that cause respiratory infections in humans and animals. Apart from vaccinations, antiviral drugs play a significant role in controlling spread of the disease. Influenza A virus contains two membrane glycoproteins on the external part of viral envelope: hemagglutinin (HA) and neuraminidase (NA), which are crucial for productive infection in target cells. In the present work, two derivatives of tunicamycin - uridine derivatives of 2-deoxy sugars (designated IW3 and IW7), which target the glycan processing steps during maturation of viral glycoproteins, were assayed for their ability to inhibit influenza A virus infection in vitro. Using the cytopathic effect (CPE) inhibition assay and viral plaque reduction assay we showed, that both IW3 and IW7 inhibitors exerted significant inhibitory effect on influenza A virus infection in MDCK cells without significant toxicity for the cells. Moreover, tested compounds selectively suppressed viral protein expression in a dose-dependent manner, suggesting that the mechanism of their antiviral activity may be similar to this shown previously for other viruses. We have also excluded the possibility that both inhibitors act at the replication step of virus life cycle. Using real-time PCR assay it was shown that IW3 and IW7 did not change the level of viral RNA in infected MDCK cells after a single round of infection. Therefore, inhibition of influenza A virus infection by uridine derivatives of 2-deoxy sugars, acting as glycosylation inhibitors, is a promising alternative approach for the development of new anti-influenza A therapy.


Assuntos
Antivirais/farmacologia , Desoxiaçúcares/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H5N2/efeitos dos fármacos , Influenza Humana/virologia , Uridina/farmacologia , Animais , Antivirais/química , Linhagem Celular , Desoxiaçúcares/química , Humanos , Vírus da Influenza A Subtipo H1N1/fisiologia , Vírus da Influenza A Subtipo H5N2/fisiologia , Influenza Humana/tratamento farmacológico , Uridina/química
9.
Antimicrob Agents Chemother ; 57(5): 2171-81, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23459475

RESUMO

Oseltamivir carboxylate (OC) has been detected in environmental waters at various levels during recent influenza seasons in humans, reflecting levels of usage and stability of this drug. In consideration of the role of waterfowl as hosts for influenza viruses that may contribute to human infections, we evaluated the effect of consumption of low doses of OC on development of oseltamivir-resistant influenza virus mutants in mallard ducks (Anas platyrhynchos) infected with two different low-pathogenic (LP) H5N2 avian influenza viruses (AIV). We detected development of virus variants carrying a known molecular marker of oseltamivir resistance (neuraminidase E119V) in 4 out of 6 mallards infected with A/Mallard/Minnesota/182742/1998 (H5N2) and exposed to 1,000 ng/liter OC. The mutation first appeared as a minor population on days 5 to 6 and was the dominant genotype on days 6 to 8. Oseltamivir-resistant mutations were not detected in virus from ducks not exposed to the drug or in ducks infected with a second strain of virus and similarly exposed to OC. Virus isolates carrying the E119V mutation displayed in vitro replication kinetics similar to those of the wild-type virus, but in vivo, the E119V virus rapidly reverted back to wild type in the absence of OC, and only the wild-type parental strain was transmitted to contact ducks. These results indicate that consumption by wild waterfowl of OC in drinking water may promote selection of the E119V resistance mutation in some strains of H5N2 AIV that could contribute to viruses infecting human populations.


Assuntos
Antivirais/farmacologia , Patos/virologia , Poluentes Ambientais/farmacologia , Vírus da Influenza A Subtipo H5N2/efeitos dos fármacos , Influenza Aviária/virologia , Neuraminidase/genética , Oseltamivir/análogos & derivados , Proteínas Virais/genética , Animais , Antivirais/sangue , Antivirais/farmacocinética , Farmacorresistência Viral/efeitos dos fármacos , Poluentes Ambientais/sangue , Poluentes Ambientais/farmacocinética , Vírus da Influenza A Subtipo H5N2/enzimologia , Vírus da Influenza A Subtipo H5N2/genética , Influenza Aviária/transmissão , Mutação , Neuraminidase/metabolismo , Oseltamivir/sangue , Oseltamivir/farmacocinética , Oseltamivir/farmacologia , Carga Viral , Proteínas Virais/metabolismo , Replicação Viral
10.
Am J Pathol ; 182(4): 1308-21, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23395090

RESUMO

Differing sensitivity of influenza A viruses to antiviral effects of the Myxovirus resistance (Mx) protein implies varying global gene expression profiles in the host. The role of Mx protein during lethal avian influenza (AI) virus infection was examined using Mx1-deficient C57BL/6 (B6-Mx1(-/-)) and congenic Mx1-expressing (B6-Mx1(+/+)) mice infected with a virulent, mouse-adapted avian H5N2 Ab/Korea/ma81/07 (Av/ma81) virus. After infection, B6-Mx1(+/+) mice were completely protected from lethal AI-induced mortality, and exhibited attenuated clinical disease and reduced viral titers and pathology in the lungs, compared with B6-Mx1(-/-) mice. Transcriptional profiling of lung tissues revealed that most of the genes up-regulated after infection are involved in activation of the immune response and host defense. Notably, more abundant and sustained expression of cytokine/chemokine genes was observed up to 3 dpi in B6-Mx1(-/-) mice, and this was associated with excessive induction of cytokines and chemokines. Consequently, massive infiltration of macrophages/monocytes and granulocytes into lung resulted in severe viral pneumonia and potentially contributed to decreased survival of B6-Mx1(-/-) mice. Taken together, our data show that dysregulated gene transcriptional activity corresponded to persistent induction of cytokine/chemokines and recruitment of cytokine-producing cells that promote inflammation in B6-Mx1(-/-) mouse lungs. Thus, we provide additional evidence of the interplay of genetic, molecular, and cellular correlates governed by the Mx1 protein that critically determine disease outcome during lethal AI virus infection.


Assuntos
Proteínas de Ligação ao GTP/metabolismo , Inflamação/patologia , Influenza Aviária/prevenção & controle , Influenza Aviária/virologia , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , Animais , Líquido da Lavagem Broncoalveolar , Galinhas , Citocinas/farmacologia , Cães , Proteínas de Ligação ao GTP/deficiência , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/complicações , Inflamação/virologia , Vírus da Influenza A Subtipo H5N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H5N2/patogenicidade , Influenza Aviária/patologia , Interferons/farmacologia , Interleucinas/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Resistência a Myxovirus , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Neutrófilos/patologia , Infecções por Orthomyxoviridae/genética , Virulência/efeitos dos fármacos
11.
Antiviral Res ; 97(3): 245-54, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23274623

RESUMO

This work continues a series of recently published studies that employ recombinant single-domain antibody (sdAb, or nanobody®) generation technologies to battle viruses by a passive immunization approach. As a proof of principle, we describe a modified technique to efficiently generate protective molecules against a particular strain of influenza virus within a reasonably short period of time. This approach starts with the immunization of a camel (Camelus bactrianus) with the specified antigen-enriched material presented in as natural a form as possible. An avian influenza virus A/Mallard/Pennsylvania/10218/84 (H5N2) adapted for mice was used as a model source of antigens for both the immunization and phage display-based selection procedures. To significantly increase activities of initially selected monovalent single-domain antibodies, we propose a new type of sdAb formatting that involves the addition of a special type of coiled-coil sequence, the isoleucine zipper domain (ILZ). Presumably, the ILZ-containing peptides adopt trimeric parallel conformations. After the formatting, the biological activities (virus neutralization) of the initially selected anti-influenza virus (H5N2) sdAbs were significantly increased. Intraperitoneal or intranasal administration of the formatted sdAb at 2h before or 24h after viral challenge specifically protects mice from lethal infection with influenza virus. We hope that the described approach combined with the selection focused on particular conservative epitopes will lead to the generation of sdAb-based molecules protective against a broad spectrum of influenza virus subtypes.


Assuntos
Anticorpos Antivirais/imunologia , Técnicas Imunológicas/métodos , Vírus da Influenza A Subtipo H5N2/fisiologia , Influenza Humana/prevenção & controle , Anticorpos de Domínio Único/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/química , Anticorpos Antivirais/genética , Camelus/genética , Camelus/imunologia , Feminino , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Vírus da Influenza A Subtipo H5N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H5N2/genética , Influenza Humana/imunologia , Influenza Humana/virologia , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Estrutura Terciária de Proteína , Anticorpos de Domínio Único/administração & dosagem , Anticorpos de Domínio Único/química , Anticorpos de Domínio Único/genética
12.
Biosci Biotechnol Biochem ; 76(3): 581-4, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22451404

RESUMO

Based on the broad-spectrum antiviral effect of green tea catechins, we established an experimental skin contact model for influenza virus transmission and evaluated the use of a green tea solution as a first-hand disinfectant. The infectivity of the virus on the skin cell layer became obsolete when washed with the green tea solution. The skin contact model could be applied to develop non-pharmaceutical intervention measures for reducing human transmission of the influenza virus.


Assuntos
Antivirais/farmacologia , Camellia sinensis/química , Desinfecção das Mãos/métodos , Extratos Vegetais/farmacologia , Animais , Linhagem Celular , Transmissão de Doença Infecciosa/prevenção & controle , Cães , Humanos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H5N2/efeitos dos fármacos , Pele/virologia , Soluções
13.
Am J Infect Control ; 39(4): 314-20, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21095042

RESUMO

BACKGROUND: Evidence has recently emerged indicating that in addition to large airborne droplets, fine aerosol particles can be an important mode of influenza transmission that may have been hitherto underestimated. Furthermore, recent performance studies evaluating airborne infection isolation (AII) rooms designed to house infectious patients have revealed major discrepancies between what is prescribed and what is actually measured. METHODS: We conducted an experimental study to investigate the use of high-throughput in-room air decontamination units for supplemental protection against airborne contamination in areas that host infectious patients. The study included both intrinsic performance tests of the air-decontamination unit against biological aerosols of particular epidemiologic interest and field tests in a hospital AII room under different ventilation scenarios. RESULTS: The unit tested efficiently eradicated airborne H5N2 influenza and Mycobacterium bovis (a 4- to 5-log single-pass reduction) and, when implemented with a room extractor, reduced the peak contamination levels by a factor of 5, with decontamination rates at least 33% faster than those achieved with the extractor alone. CONCLUSION: High-throughput in-room air treatment units can provide supplemental control of airborne pathogen levels in patient isolation rooms.


Assuntos
Microbiologia do Ar , Descontaminação/métodos , Desinfecção/métodos , Carga Bacteriana , Infecção Hospitalar/prevenção & controle , Humanos , Vírus da Influenza A Subtipo H5N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H5N2/isolamento & purificação , Mycobacterium bovis/efeitos dos fármacos , Mycobacterium bovis/isolamento & purificação , Isoladores de Pacientes , Carga Viral
14.
J Clin Virol ; 45(2): 119-24, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19406687

RESUMO

BACKGROUND: Respiratory infections caused by viruses are major causes of upper and lower respiratory tract infections. They account for an important mortality and morbidity worldwide. Amongst these viruses, influenza viruses and paramyxoviruses are major pathogens. Their transmission is mainly airborne, by direct transmission through droplets from infected cases. OBJECTIVES: In the context of an influenza pandemic, as well as for the reduction of nosocomial infections, systems that can reduce or control virus transmission will reduce the burden of this disease. It may also be part of the strategy for pandemic mitigation. STUDY DESIGN: A new system based on physical decontamination of surface and air has been developed. This process generates cold oxygen plasma (COP) by subjecting air to high-energy deep-UV light. To test its efficiency, we have developed an experimental device to assess for the decontamination of nebulized respiratory viruses. High titer suspensions of influenza virus type A, human parainfluenza virus type 3 and RSV have been tested. RESULTS: Different experimental conditions have been evaluated against these viruses. The use of COP with an internal device allowed the best results against all viruses tested. We recorded a reduction of 6.5, 3.8 and 4 log(10) TCID50/mL of the titre of the hPIV-3, RSV and influenza virus A (H5N2) suspensions. CONCLUSIONS: The COP technology is an efficient and innovative strategy to control airborne virus dissemination. It could successfully control nosocomial diffusion of respiratory viruses in hospital setting, and could be useful for the reduction of influenza transmission in the various consultation settings implemented for the management of cases during a pandemic.


Assuntos
Desinfetantes/farmacologia , Desinfecção/métodos , Microbiologia Ambiental , Vírus da Influenza A Subtipo H5N2/efeitos dos fármacos , Viabilidade Microbiana/efeitos dos fármacos , Oxigênio/farmacologia , Vírus da Parainfluenza 3 Humana/efeitos dos fármacos , Animais , Linhagem Celular , Cães , Haplorrinos
15.
Arch Virol ; 153(5): 945-9, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18227965

RESUMO

To determine the influence of oseltamivir phosphate (Tamiflu) on the results of microneutralization and hemagglutinin-inhibition (HI) tests in human sera with H5N2 influenza virus, ten volunteers were administered Tamiflu and blood samples were collected. In the microneutralization test, no consistent effects were observed. However, in the HI test, specimens from all volunteers taken at 4 and 7 h after drug administration showed a higher titer as compared to 0 and 24 h after administration when mammalian cells (horse, guinea pig, and human) were used. These results suggest that the administration of Tamiflu may affect the results of HI tests for H5N2 virus.


Assuntos
Antivirais/sangue , Testes de Inibição da Hemaglutinação , Vírus da Influenza A Subtipo H5N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H5N2/isolamento & purificação , Testes de Neutralização , Oseltamivir/sangue , Adulto , Animais , Anticorpos Antivirais/sangue , Feminino , Cobaias , Cavalos , Humanos , Vírus da Influenza A Subtipo H5N2/imunologia , Influenza Humana/diagnóstico , Influenza Humana/imunologia , Influenza Humana/virologia , Japão , Masculino , Pessoa de Meia-Idade
16.
Vopr Virusol ; 50(6): 32-5, 2005.
Artigo em Russo | MEDLINE | ID: mdl-16408629

RESUMO

The effect of the antiviral drug arbidol on the reproduction of avian influenza A/H5 viruses was studied in in vitro experiments. The strains were isolated from the wild birds of Eastern Siberia and they were closely related to the 1997-2000 viruses from South-Eastern Asia. Arbidol was shown to exert a selective inhibiting effect on the reproduction of these viruses in the MDCH cell cultures.


Assuntos
Antivirais/farmacologia , Indóis/farmacologia , Vírus da Influenza A Subtipo H5N2/efeitos dos fármacos , Animais , Animais Selvagens/virologia , Aves/virologia , Linhagem Celular , Cães , Relação Dose-Resposta a Droga , Vírus da Influenza A Subtipo H5N2/fisiologia , Influenza Aviária/virologia , Testes de Sensibilidade Microbiana , Replicação Viral/efeitos dos fármacos
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